On Monday, August 23, the National Institutes of Health held a special telebriefing for the world’s press to announce publication of the long-awaited ‘positive’ article by NIH, FDA and Harvard Medical School researchers reporting evidence of a novel retrovirus in Chronic Fatigue Syndrome patients’ blood.
Following several ‘negative’ articles reporting failure to reproduce the WPI team’s Oct 2009 Science article linking XMRV to ME/CFS, this new article set off a whirlwind of press releases, articles and blogs that may not abate for weeks – and it did not disappoint.
A transcript of the briefing is now available on the WPI website – www.wpinstitute.org/news/docs/FDAbriefing_082310.pdf.
The article – "Detection of MLV-related virus gene sequences in blood of patients with Chronic Fatigue Syndrome and healthy controls" in PDF format) – was published online Monday afternoon by the Proceedings of the National Academy of Sciences.
The (Good) Surprise
The surprise, for most of the ME/CFS world, was that these researchers found evidence of several very closely related retroviruses – part of a 'family' that includes XMRV, and dubbed “MLV-like viruses” – in 32 of the 37 ME/CFS patient blood samples, and 3 of the 44 control samples from ‘healthy’ blood donors. (MLV stands for "murine leukemia virus" and in mice MLV is known to cause neurological problems & cancer.)
The researchers consider this sufficient evidence to demonstrate “a strong association between a diagnosis of CFS and the presence of MLV-like virus gene sequences in the blood,” and to raise questions about the donated blood supply. As for the several MLV-like viruses detected, that is not surprising, the researchers commented, since retroviruses – the HIV virus, for example – do tend to mutate.(1) Importantly, while the newly discovered MLV-like retroviruses and XMRV are 96.6% similar, the XMRV retrovirus is xenotropic (can infect humans/primates but is not equipped to infect mice), while the MLV-like cousins are "polytropic," which means they are equipped to infect both mice and other species.(2)
In the researchers' words, "Although we find evidence of a broader group of MLV-related viruses, rather than just XMRV, in patients with CFS and healthy blood donors, our results clearly support the central argument by Lombardi et al. [the 2009 Science article] that MLV-related viruses are associated with CFS and are present in some blood donors."
The authors include Dr. Harvey J. Alter, Chief of the NIH’s Infectious Diseases Section; four investigators from the FDA’s Center for Biologics Evaluation and Research including lead investigator Dr. Shyh-Ching Lo, an internationally recognized HIV research expert; and Dr. Anthony Komaroff, an ME/CFS physician researcher at Harvard Medical School who has studied the viral dimension of the illness for decades. Dr. Komaroff had banked 25 of the blood samples from his ME/CFS patients 15 years ago. And importantly, analysis of fresh samples from 8 of these patients found that 7 still were positive for HLV-like viruses, though the viruses had changed over that time, as might be expected in this "quickly evolving" type of virus.
The Scoop on the Scoop, by ME/CFS Reporter Mindy Kitei
For an excellent, easy-to-read explanation of this paper’s meaning, plus plenty of well-researched "back story," be sure to read Mindy Kitei’s article, “The FDA/NIH/Harvard ‘XMRV’ study: The same thing, only different,” at www.CFSCentral.com.
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The article is a model of careful investigative work, enriched by Mindy’s confidential interviews with the authors and others before the story broke.
Tests for XMRV & Variants? Available Now Online
Also on Friday, Aug 23, the VIP Dx laboratory (formerly RedLabs USA), which licenses the test technology from the WPI, announced that patients can now order tests online for “XMRV & Variants” (read MLV-like viruses?).
Clearly, more and larger studies of different patient cohorts are needed, just for starters, to:
• Determine how the MLV-like retrovirus gang is associated with ME/CFS – cause, or not?
• Understand the size and nature of the ME/CFS subset that may be involved.
• Discover whether transmission is possible via the blood. (As Kitei points out, studies at Emory University’s Yerkes Primate Research Center indicate antibodies to XMRV can be produced in rhesus macaque monkeys after infection by intravenous inoculation.)
• Look for "HLV-like" viruses in patients with other illnesses. Dr. Alter told Kitei he will be looking at cohorts of patients with fibromyalgia, HIV, Hepatitis C, and autoimmune diseases as well as ME/CFS.
• Conduct anti-viral trials. Commenting on the new findings and lack of consensus on which/whether/how viruses are related to ME/CFS, a number of scientists suggest the real challenge now is finding anti-retroviral therapies that produce good results for patients. They noted that nobody accepted the previously undiscovered bug Helicobacter pylori as the cause of peptic ulcers ('common knowledge' and a major source of pharmaceutical income supported stress as the cause) until it was proved that antibiotics healed the ulcers. They note too that participating in such trials can involve clear risks and is not to be undertaken lightly.
New Era of Interest and Hope
But as of August 23, 2010 we can be assured that the spotlights of research funding and talent will focus as never before on ME/CFS – its cause and its cure. Within hours of the article's release, more than 100 news sources had covered the story, including the Wall Street Journal (online report by Amy Dockser Marcus, followed by front page placement Tuesday morning), New York Times, Business Week, Washington Post, National Public Radio, CNN, San Francisco Chronicle, and Scientific American, as well as ME/CFS advocacy organizations such as the CFIDS Association ("Another Turn of the Retrovirus Kaleidoscope").
1. This week, for example, HIV/AIDS researchers at the University of North Carolina reported such a mutation. See “Just discovered: HIV retrovirus in male genital tract strikingly different from ‘known’ form found in blood.”
2. See the accompanying PNAS article "Mouse retroviruses and chronic fatigue syndrome: Does X (or P) mark the spot?"